1. Field of the Invention
The present invention relates to a novel method of administering the natural female sex hormones, 17.beta.-estradiol and progesterone, and to novel dosage forms containing those compounds, singly or in combination, which are adapted for nasal administration.
2. Description of the Prior Art
17.beta.-estradiol is the most potent natural estrogen found in human beings and is the major secretory product of the ovary. It is readily oxidized in the body to estrone, which in turn can be hydrated to estriol. These transformations take place mainly in the liver, where there is free interconversion between estrone and estradiol. All three of these natural estrogens are excreted in the urine as glucuronides and sulfates, along with a host of related, minor products in water-soluble complexes. It is widely known that, following oral administration of micronized 17.beta.-estradiol (E.sub.2), the incremental circulation estrogen is principally the less active species estrone (E.sub.1), which reaches a peak concentration many times greater than that of E.sub.2. The conversion of E.sub.2 to E.sub.1 and subsequently to other metabolites takes place during absorption from the intestine and passage through the liver. This extensive metabolism greatly limits the oral effectiveness of the natural estrogens and their esters. Indeed, because of their limited oral efficacy, 17.beta.-estradiol and its esters are generally administered by intramuscular injection.
Progesterone is the active natural progestin which occurs in the corpus luteum, placenta and adrenal cortex. It is not effective by mouth because of its rapid metabolism in the intestinal epithelium and in the liver, and is therefore only administered intramuscularly.
Because of their limited oral effectiveness, these natural female sex hormones have not found utility in oral contraceptives. Instead, only active synthetic estrogens and progestins have been prepared and are used for contraceptive purposes. The synthetic derivatives have also in many cases replaced the natural substances in the treatment of menopause, threatened abortion, etc. However, the synthetic derivatives are, generally speaking, much more likely to cause toxic side effects than are the relatively safe natural hormones.